Very limited medical and surgical options are available for treating laryngeal pathologies characterized by tissue damage and deficiencies in the vocal fold lamina propria, largely due to the fact that an optimal, surgically implantable biomaterial for reconstruction of the vocal fold lamina propria extracellular matrix (ECM) has yet to be developed. Such a material should have biomechanical properties and vibratory properties similar to those of the lamina propria ECM, in order to facilitate functional phonatory performance of the vocal fold. It should also be able to simulate the complex composition of the vocal fold ECM, as well as provide relatively long-lasting augmentation while allowing for new tissue formation and constructive remodeling. In our preliminary studies, we have developed a novel acellular, xenogeneic tissue engineering scaffold derived from the bovine vocal fold lamina propria. The overarching goal of this project is to examine the in vivo potential of this biological ECM scaffold, specifically in terms of the prevention and reduction of lamina propria disorders, and the maintenance and restoration of normal viscoelasticity of the lamina propria ECM for functional vibratory performance. For the proposed funding period, we will focus on determining the efficacy of the bovine acellular scaffold for the prevention of vocal fold scarring in vivo, when it is being implanted into the lamina propria immediately after induced vocal fold injury in a rabbit model. Furthermore, we will explore the potential of the bovine acellular scaffold for the treatment of vocal fold scarring in vivo, when it is being implanted into the lamina propria three days after injury in the rabbit model. Quantitative methodologies will be used to compare the tissue composition, protein organization, and viscoelastic properties of the treated vocal fold at different time points to those of the contralateral intact or untreated injured vocal fold. In the proposed studies, we will test the overall hypothesis that the biological acellular ECM scaffold derived from the bovine vocal fold lamina propria can be used as an implantable tissue substitute for surgical reconstruction of the damaged vocal fold lamina propria in vivo. PUBLIC HEALTH RELEVANCE: Each year, an estimated 3-9% of Americans suffer from some kind of voice disorders, which adversely affect the communicative abilities, quality of life, and even the careers of individuals relying on a healthy, functional voice for their occupations. Despite the recent advances in phonosurgical approaches and therapeutic strategies, vocal fold lamina propria defects, such as vocal fold scarring, atrophy and sulcus vocalis, remain to be among the most clinically challenging disorders, due to the vulnerability of the vocal fold lamina propria to scar tissue formation and the difficulties to effectively replace the lamina propria. The proposed research explores the potential of an innovative tissue engineering scaffold to facilitate the functional reconstruction of the injured vocal fold lamina propria, and could contribute to the development of effective surgical management for such voice disorders.